US7713705B2 - Markers for differential diagnosis and methods of use thereof - Google Patents
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- US7713705B2 US7713705B2 US10/330,696 US33069602A US7713705B2 US 7713705 B2 US7713705 B2 US 7713705B2 US 33069602 A US33069602 A US 33069602A US 7713705 B2 US7713705 B2 US 7713705B2
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Abstract
Description
Rj=ΣwiIi,j,
where i is the marker index, j is the subject index, wi is the weighting coefficient for marker i, I is the indicator value to which the marker level for marker i is mapped for subject j, and Σ is the summation over all candidate markers i.
Condition | Marker | ||
Acute Coronary Syndrome | Haptoglobin | ||
Acute Coronary Syndrome | S100a | ||
Acute Coronary Syndrome | s-CD40 ligand | ||
Acute Coronary Syndrome | S-FAS ligand | ||
Aortic dissection | alpha 2 actin | ||
Aortic dissection | basic calponin 1 | ||
Aortic dissection | beta like 1 integrin | ||
Aortic dissection | CSRP2 | ||
Aortic dissection | elastin | ||
Aortic dissection | LTBP4 | ||
Aortic dissection | smooth muscle myosin | ||
Aortic dissection | transgelin | ||
Aortic dissection | MMP1 | ||
Aortic dissection | MMP2 | ||
Aortic dissection | MMP3 | ||
Diastolic dysfunction | aldosterone | ||
Diastolic dysfunction | angiotensin 1 | ||
Diastolic dysfunction | angiotensin 2 | ||
Diastolic dysfunction | angiotensin 3 | ||
Diastolic dysfunction | Bradykinin | ||
Diastolic dysfunction | calcitonin | ||
Diastolic dysfunction | calcitonin gene related peptide | ||
Diastolic dysfunction | Endothelin-2 | ||
Diastolic dysfunction | Endothelin-3 | ||
Diastolic dysfunction | Renin | ||
diastolic dysfunction/sepsis | Vasopressin | ||
pancreatitis | APO B48 | ||
pancreatitis | pancreatic elastase 1 | ||
pancreatitis | pancreatic Lipase | ||
pancreatitis | sPLA2 | ||
pancreatitis | Trypsinogen activation peptide | ||
pulmonary embolism | alpha enolase | ||
pulmonary embolism | LAMP3 | ||
pulmonary embolism | phospholipase D | ||
pulmonary embolism | PLA2G5 | ||
pulmonary embolism | Protein D | ||
pulmonary embolism | SFTPC | ||
pulmonary embolism | Defensin HBD 1 | ||
pulmonary embolism | Defensin HBD 2 | ||
pulmonary embolism | CXC-type chemokines | ||
(CXCL-1, CXCL-2, CXCL-3) | |||
pulmonary embolism | CC-type chemokines | ||
(CCL2, CCL3, CCL4, CCL8) | |||
pulmonary embolism | Endothelin 1 | ||
sepsis | Defensin HBD 1 | ||
sepsis | Defensin HBD 2 | ||
sepsis | D-dimer | ||
sepsis | iL-1 | ||
sepsis | iL-10* | ||
sepsis | iL-11* | ||
sepsis | iL-13* | ||
sepsis | iL-18* | ||
sepsis | iL-4* | ||
sepsis | Procalcitonin | ||
sepsis | PROTEIN C | ||
sepsis | Serum Amyloid A | ||
sepsis | s-Glutathione | ||
sepsis | s-iL 18 receptor | ||
sepsis | S-iL-1 receptor | ||
sepsis | s-TNF P55 | ||
sepsis | s-TNF P75 | ||
sepsis | TAFI | ||
sepsis | TGF-beta | ||
sepsis | MMP-11 | ||
stroke | Brain Fatty acid binding protein | ||
stroke | CA11 | ||
stroke | CABP1 | ||
stroke | CACNA1A | ||
stroke | CBLN1 | ||
stroke | CHN1 | ||
stroke | CHN2 | ||
stroke | cleaved Tau | ||
stroke | CRHR1 | ||
stroke | DRPLA | ||
stroke | EGF | ||
stroke | Endothelin-1 | ||
stroke | GFAP | ||
stroke | GPM6B | ||
stroke | GPR7 | ||
stroke | GPR8 | ||
stroke | GRIN2C | ||
stroke | GRM7 | ||
stroke | HAPIP | ||
stroke | HIF 1 ALPHA | ||
stroke | HIP2 | ||
stroke | KCNK4 | ||
stroke | KCNK9 | ||
stroke | KCNQ5 | ||
stroke | MAPK10 | ||
stroke | n-acetyl aspartate | ||
stroke | NEUROD2 | ||
stroke | NRG2 | ||
stroke | PACE4 | ||
stroke | phosphoglycerate mutase | ||
stroke | PKC gamma | ||
stroke | Prostaglandin E2 | ||
stroke | PTEN | ||
stroke | PTPRZ1 | ||
stroke | RGS9 | ||
stroke | SCA7 | ||
stroke | secretagogin | ||
stroke | SLC1A3 | ||
stroke | SORL1 | ||
stroke | SREB3 | ||
stroke | STAC | ||
stroke | STX1A | ||
stroke | STXBP1 | ||
stroke/migraine | BDNF* | ||
stroke/migraine | CGRP | ||
stroke/migraine | cystatin C | ||
stroke/migraine | neurokinin A | ||
stroke/migraine | substance P | ||
TABLE 1 |
Multi-Center CHF Patients |
Patient ID | PSD | D-Dimer | BNP | Tnl | Ratio | ||
16 | 35.4 | 88 | 889 | 2.1 | 10.1 | ||
012 | 8.7 | 113 | 1228 | 2.2 | 10.9 | ||
Moore 003 | 6.9 | 62 | 552 | 0.0 | 8.9 | ||
11 | 11.7 | 160 | 987 | 0.5 | 6.2 | ||
010 | 13.3 | 145 | 466 | 0.0 | 3.2 | ||
18 | 7.9 | 39 | 330 | 0.0 | 8.6 | ||
131-2 | 7.2 | 125 | 1031 | 0.0 | 8.3 | ||
125-1 | 3.7 | 49 | 314 | 0.0 | 6.4 | ||
115 | 8.1 | 203 | 185 | 0.0 | 0.9 | ||
128-1 | 7.5 | 141 | 228 | 0.0 | 1.6 | ||
143-1 | 5.1 | 169 | 402 | 0.0 | 2.4 | ||
134-1 | 1.9 | 142 | 251 | 0.0 | 1.8 | ||
138-1 | 2.4 | 40 | 521 | 0.0 | 13.0 | ||
157-1 | 4.1 | 107 | 231 | 0.0 | 2.2 | ||
176-1 | 2.6 | 70 | 234 | 0.0 | 3.4 | ||
175-1 | 4.6 | 154 | 498 | 0.0 | 3.2 | ||
22 | 6.7 | 36 | 650 | 0.0 | 18.3 | ||
21 | 3.9 | 149 | 453 | 0.0 | 3.0 | ||
23 | 11.5 | 147 | 1024 | 0.0 | 7.0 | ||
103-2 | 3.3 | 70 | 640 | 0.0 | 9.2 | ||
20 | 2.9 | 78 | 858 | 0.0 | 11.0 | ||
148-2 | 6.2 | 79 | 1614 | 0.0 | 20.4 | ||
173-2 | 2.7 | 68 | 236 | 0.0 | 3.5 | ||
166-1 | 5.5 | 53 | 681 | 0.0 | 12.9 | ||
178-1 | 4.3 | 89 | 250 | 0.0 | 2.8 | ||
183-2 | 9.3 | 109 | 1199 | 0.0 | 11.0 | ||
189-2 | 2.2 | 270 | 335 | 0.0 | 1.2 | ||
42 | 3.5 | 143 | 846 | 0.0 | 5.9 | ||
43 | 4.2 | 63 | 287 | 0.0 | 4.5 | ||
54 | 3.5 | 51 | 302 | 0.0 | 5.9 | ||
25 | 4.6 | 61 | 768 | 0.0 | 12.5 | ||
53 | 4.5 | 77 | 1813 | 0.0 | 23.5 | ||
59 | 20.8 | 77 | 288 | 0.0 | 3.7 | ||
55 | 2.4 | 53 | 237 | 0.0 | 4.5 | ||
158-1 | 2.3 | 53 | 1030 | 0.0 | 19.6 | ||
Mean | 6.7 | 100.9 | 624.5 | 0.1 | 7.8 | ||
Median | 4.6 | 79.3 | 498.0 | 0.0 | 6.2 | ||
St. Dev. | 6.3 | 53.1 | 415.8 | 0.5 | 5.9 | ||
TABLE 2 |
Multi-Center Patients with PE |
Patient ID | PSD | D-Dimer | BNP | Tnl | Ratio | ||
81 | 4.9 | 145 | 314.7 | 0.0 | 2.2 | ||
110 | 4.3 | 87 | 24.3 | 0.0 | 0.3 | ||
112 | 6.9 | 105 | 15.9 | 0.0 | 0.2 | ||
119 | 10.1 | 104 | 175.7 | 0.0 | 1.7 | ||
142 | 7.0 | 106 | 6.2 | 0.0 | 0.1 | ||
196 | 8.2 | 127 | 5.0 | 0.1 | 0.0 | ||
801-2 | 5.2 | 113 | 19.7 | 0.0 | 0.2 | ||
377-2 | 1.4 | 97 | 57.2 | 0.0 | 0.6 | ||
008264 | 1.3 | 258 | 121.3 | 0.0 | 0.5 | ||
008557 | 17.5 | 126 | 51.3 | 0.0 | 0.4 | ||
010647 | 3.8 | 106 | 355.3 | 0.0 | 3.4 | ||
10640 | 0.7 | 43 | 9.2 | 0.0 | 0.2 | ||
7329 | 3.4 | 191 | 287.3 | 0.0 | 1.5 | ||
008605 | 6.0 | 82 | 733.5 | 0.0 | 9.0 | ||
Mean | 5.8 | 120.7 | 155.5 | 0.0 | 1.4 | ||
Median | 5.0 | 105.7 | 54.3 | 0.0 | 0.4 | ||
St. Dev. | 4.3 | 51.7 | 207.6 | 0.0 | 2.4 | ||
TABLE 3 |
Normal Subjects |
Patient ID | PSD | D-Dimer | BNP | Tnl | Ratio | ||
001511 | 5.1 | 90 | 20.4 | 0.0 | 0.2 | ||
001515 | 1.9 | 36 | 8.9 | 0.0 | 0.2 | ||
001520 | 1.0 | 61 | 6.5 | 0.0 | 0.1 | ||
001521 | 4.6 | 72 | 3.8 | 0.0 | 0.1 | ||
001524 | 2.3 | 69 | 11.1 | 0.0 | 0.2 | ||
001607 | 3.6 | 72 | 23.4 | 0.0 | 0.3 | ||
001610 | 1.1 | 52 | 18.3 | 0.0 | 0.4 | ||
001613 | 0.2 | 40 | 0.0 | 0.0 | 0.0 | ||
001616 | 2.6 | 28 | 0.0 | 0.0 | 0.0 | ||
001619 | 0.3 | 44 | 0.0 | 0.0 | 0.0 | ||
001622 | 1.4 | 25 | 0.0 | 0.0 | 0.0 | ||
001625 | 4.6 | 142 | 0.0 | 0.0 | 0.0 | ||
001628 | 1.6 | 40 | 0.0 | 0.0 | 0.0 | ||
001631 | 4.6 | 57 | 0.0 | 0.0 | 0.0 | ||
001634 | 7.2 | 60 | 6.6 | 0.0 | 0.1 | ||
001637 | 5.5 | 55 | 0.0 | 0.0 | 0.0 | ||
001640 | 0.0 | 260 | 19.1 | 0.0 | 0.1 | ||
001643 | 2.5 | 50 | 7.7 | 0.0 | 0.2 | ||
001646 | 0.0 | 56 | 4.7 | 0.0 | 0.1 | ||
002202 | 1.0 | 59 | 27.4 | 0.0 | 0.5 | ||
002205 | 1.7 | 39 | 23.4 | 0.0 | 0.6 | ||
002208 | 1.1 | 25 | 25.9 | 0.0 | 1.0 | ||
002211 | 0.9 | 55 | 45.9 | 0.0 | 0.8 | ||
002214 | 0.0 | 97 | 23.4 | 0.0 | 0.2 | ||
002217 | 2.8 | 117 | 15.3 | 0.0 | 0.1 | ||
002220 | 0.3 | 55 | 11.3 | 0.0 | 0.2 | ||
002223 | 2.5 | 47 | 8.1 | 0.0 | 0.2 | ||
002228 | 2.2 | 44 | 24.3 | 0.0 | 0.5 | ||
002229 | 2.6 | 61 | 11.2 | 0.0 | 0.2 | ||
002232 | 0.7 | 69 | 10.5 | 0.0 | 0.2 | ||
002235 | 0.0 | 54 | 4.0 | 0.0 | 0.1 | ||
002238 | 1.5 | 53 | 9.6 | 0.0 | 0.2 | ||
002241 | 7.5 | 16 | 10.8 | 0.0 | 0.7 | ||
002244 | 8.6 | 44 | 10.7 | 0.0 | 0.2 | ||
002247 | 3.7 | 68 | 33.1 | 0.0 | 0.5 | ||
Mean | 2.5 | 63.3 | 12.2 | 0.0 | 0.2 | ||
Median | 1.9 | 55.0 | 10.5 | 0.0 | 0.2 | ||
St. Dev. | 2.3 | 42.3 | 11.1 | 0.0 | 0.3 | ||
Class | Functional Capacity | Objective Assessment |
NYHA1 | Patients with cardiac disease but | No objective |
without resulting limitation of | evidence of | |
physical activity. Ordinary physical | cardiovascular | |
activity does not cause undue | disease. | |
fatigue, palpitation, dyspnea, | ||
or anginal pain. | ||
NYHA2 | Patients with cardiac disease resulting in | Objective |
slight limitation of physical activity. | evidence of | |
They are comfortable at rest. Ordinary | minimal | |
physical activity results in fatigue, | cardiovascular | |
palpitation, dyspnea, or anginal pain. | disease. | |
NYHA3 | Patients with cardiac disease resulting | Objective |
in marked limitation of physical | evidence | |
activity. They are comfortable at rest. | of moderately | |
Less than ordinary activity causes | severe | |
fatigue, palpitation, dyspnea, or anginal | cardiovascular | |
pain. | disease. | |
NYHA4 | Patients with cardiac disease resulting | Objective |
in inability to carry on any physical | evidence | |
activity without discomfort. Symptoms | of severe | |
of heart failure or the anginal syndrome | cardiovascular | |
may be present even at rest. If any | disease. | |
physical activity is undertaken, | ||
discomfort is increased. | ||
TABLE 4 | |||||||
Vaso- | Endothelin | BNP/ | Calci- | ||||
BNP | pressin | 2 | CGRP | CGRP | tonin | ||
Normal | 0 | 0.98 | 3.60 | 0.94 | 0 | 0.14 |
DD NYHA1 | 142 | 1.13 | 4.63 | 1.06 | 247 | 0.20 |
DD NYHA2 | 152 | 0.89 | 3.70 | 0.77 | 289 | 0.19 |
DD NYHA3 | 325 | 0.84 | 3.72 | 1.02 | 309 | 0.16 |
DD NYHA4 | 600 | 0.99 | 4.38 | 0.66 | 853 | 0.17 |
DD All | 262 | 0.89 | 3.91 | 0.77 | 366 | 0.19 |
Low EF | 839 | 1.10 | 4.38 | 0.97 | 957 | 0.19 |
Urotensin | BNP/ | BNP/ | Angiotensin | ||||
2 | U2 | ANP | ANP | 2 | N | ||
Normal | 14.6 | 0 | 1.84 | 0 | 0.09 | 20 |
DD NYHA1 | 18.9 | 11 | 2.11 | 162 | 0.09 | 2 |
DD NYHA2 | 18.4 | 9 | 1.48 | 113 | 0.08 | 6 |
DD NYHA3 | 18.8 | 16 | 1.95 | 149 | 0.09 | 6 |
DD NYHA4 | 19.8 | 30 | 1.07 | 297 | 0.06 | 6 |
DD All | 19.0 | 14 | 1.50 | 177 | 0.08 | |
Low EF | 28.0 | 41 | 2.17 | 413 | 0.07 | 20 |
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US10/330,696 US7713705B2 (en) | 2002-12-24 | 2002-12-27 | Markers for differential diagnosis and methods of use thereof |
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US10/728,067 US20040203083A1 (en) | 2001-04-13 | 2003-12-03 | Use of thrombus precursor protein and monocyte chemoattractant protein as diagnostic and prognostic indicators in vascular diseases |
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PCT/US2003/041453 WO2004059293A2 (en) | 2002-12-24 | 2003-12-23 | Markers for differential diagnosis and methods of use thereof |
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